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Atorvastatin alleviates left ventricular remodeling in isoproterenol-induced chronic heart failure in rats by regulating the RhoA/Rho kinase signaling pathway
- Source :
- Pharmacological Reports; 20240101, Issue: Preprints p1-9, 9p
- Publication Year :
- 2024
-
Abstract
- Background: Chronic heart failure (CHF) is characterized by left ventricular dysfunction and altered autonomic control of cardiac function. This study aimed to investigate the effects of atorvastatin on left ventricular remodeling (LVR) and cardiac function in rats with isoproterenol-induced CHF and the possible mechanism. Methods: An isoproterenol-induced CHF model was established in rata, which were subsequently treated with atorvastatin. Echocardiography, hemodynamic, and left ventricular mass indexes were assessed. The mRNA expression of RhoA, Rho kinase, and endothelial nitric oxide synthase (eNOS) was determined by RT-qPCR. The protein expression of myosin-binding subunit (MBS), MBS-P, eNOS, phosphorylated-eNOS, RhoA, and Rho kinase was measured by Western blot analysis. The relative activity of NADPH oxidase, ROS, and NO was assessed by ELISA. Results: Isoproterenol-induced CHF rats treated with atorvastatin exhibited decreased left ventricular end-systolic dimension, left ventricular end-diastolic dimension, left ventricular end-diastolic pressure, left ventricular mass index, maximum fall rate of change in left ventricular pressure, heart rate (p< 0.001), expression of RhoA, Rho kinase, MBS and MBS-P (p< 0.01), and relative activity of NADPH oxidase, ROS and NO (p< 0.05) and increased left ventricular short axis fractional shortening, left ventricular end-systolic pressure, maximum rise rate of change in left ventricular pressure (p< 0.001) and expression of eNOS, and phosphorylated-eNOS ser1177 (all p< 0.05) compared with those of rats with isoproterenol-induced CHF. Conclusion: We demonstrated that atorvastatin inhibits LVR and improves cardiac function in rats with isoproterenol-induced CHF through inhibition of the RhoA/Rho kinase signaling pathway.
Details
- Language :
- English
- ISSN :
- 17341140 and 22995684
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Pharmacological Reports
- Publication Type :
- Periodical
- Accession number :
- ejs52619932
- Full Text :
- https://doi.org/10.1007/s43440-020-00085-3